Intrauterine growth retardation is a common clinical problem, yet the origins of this condition, as well as preventive measures, have not yet been determined. IUGR can be modeled in rodents by a variety of techniques, one of which is administration of epidermal growth factor (EGF) to newborn rats for a period of 72 hours. Such rats are permanently growth retarded, with the liver and kidney demonstrating a marked reduction in size after this treatment. The major hypothesis to be examined in the proposal is that injection of neonatal rats with EFG alters the normal ontogenic expression of growth factors in the liver and kidney, which leads to a reduced mass of these organs. It has previously been demonstrated that both the kidney and liver produce multiple types of growth factors; for the current study we will concentrate on the basic and acidic fibroblast growth factor (FGFs) and transforming growth factor beta 1 (TGF- beta1). These growth factors are ubiquitous, and have been implicated in early embryonal development and angiogenesis. In order to test the overall hypothesis the following specific aims and subhypotheses will be pursued. The first is that there is a normal ontogenic pattern of expression of the FGFs and TGF-beta1 in the development rat liver and kidney, both at the protein and mRNA levels. The second is that specific cell types within the liver and kidney are producing these growth factors, which will be determined using both immunohistochemical and in-situ hybridization techniques. The third is that the cells expressing the FGFs and TGF-beta1 will express receptors for these factors, and that receptor expression may be altered during development. The effects of neonatal EGF treatment on the normal ontogenic patterns observed will be determined for each of these specific aims. The data obtained from these studies will be informative concerning the role of growth factors during development and the process of growth retardation, and should allow for a refined hypothesis to be developed concerning the role of these growth factors in liver and kidney organogenesis.